This research will be done primarily in Australia and Malawi as an extension of NIH grant number 1 R01. More than 90 percent of all malaria infections and more than two thirds of all HIV infections in the world occur in sub Saharan Africa. Important interactions between HIV-1 and malaria have been identified: co-infectedb persons have 7-fold higher viral loads than those with HIV-1 alone. In pregnant women, malaria is associated with an infiltrate of monocytes into the placenta. This proposal extends an existing NIH study by characterising the observed monocytic infiltrate in the placenta of pregnant women in Malawi and assessing the potential contribution of these cells to maternal HIV-1 viral load and thus to mother-to-child transmission (MTCT) of HIV-1. Our hypothesis is that malarial infection causes the expansion of a minority subset of peripheral blood monocytes which has higher CCR5 surface expression than the majority of peripheral blood monocytes and is thus more susceptible to HIV infection. We predict that women co-infected with malaria and HIV-1 have higher HIV-1 viral loads and higher mother-to-child transmission of HIV-1 than women with HIV-1 alone. To examine this, we will perform a nested study within the existing cohort study of HIV positive pregnant women enrolled in the parent NIH study in Blantyre, Malawi. Monocyte subsets (CD14hi and CD14dim/CDI 6hi) will be identified by flow cytometric analysis in peripheral blood, placental blood and cord blood samples of HIV positive/malaria positive, HIV positive/malaria negative women and controls. Results will be correlated with maternal viral load and MTCT of HIV-1. The results of this study will promote our understanding of the pathogenesis of mother-to-child transmission of HIV-1.